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#9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria


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Abstract
Plant-derived cannabinoids, including
#9-tetrahydrocannabinol (THC), induce apoptosis in
leukemic cells, althoughthe precise mechanism remains
unclear. In the current study, we investigated the effect
of THC on the upstream and downstream events that
modulate the extracellular signal-regulated kinase (ERK)
module of mitogen-activated protein kinase pathways
primarily in human Jurkat leukemia T cells. The
data showed that THC down-regulated Raf-1/mitogenactivated
protein kinase/ERK kinase (MEK)/ERK/RSK
pathwayleadingtotranslocationofBadtomitochondria.
THC also decreased the phosphorylation of Akt.
However, no significant association of Bad translocation
with phosphatidylinositol 3-kinase/Akt and protein
kinase A signaling pathways was noted when treated
cells were examined in relation to phosphorylation
status of Bad by Western blot and localization of Bad to
mitochondria by confocal analysis. Furthermore, THC
treatment decreased the Bad phosphorylation at Ser112
but failed to alter the level of phospho-Bad on site
Ser136 that has been reported to be associated with
phosphatidylinositol3-kinase/Aktsignalpathway.Jurkat
cells expressing a constitutively active MEK construct
were found to be resistant to THC-mediated apoptosis
and failed to exhibit decreased phospho-Bad on Ser112
as well as Bad translocation to mitochondria. Finally,
useofBad smallinterferingRNAreducedtheexpression
of Bad in Jurkat cells leading to increased resistance
to THC-mediated apoptosis. Together, these data
suggested that Raf-1/MEK/ERK/RSK-mediated Bad translocationplayedacriticalroleinTHC-inducedapoptosis
in Jurkat cells. (Mol Cancer Res 2006;4(8):549â62)

http://mcr.aacrjournals.org/content/4/8/549.full


Language English
Collection opensource

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